Vorolanib + Atezolizumab for Small Cell Lung Cancer

No longer recruiting at 1 trial location

Overseen By Daniel Morgensztern

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Platinum, Etoposide, Atezolizumab

Must not be taking: NSAIDs, Glucocorticoids, Antiplatelets

Disqualifiers: Other malignancy, Untreated brain metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding vorolanib to atezolizumab (Tecentriq) can help people with small cell lung cancer remain cancer-free longer after standard chemotherapy. Participants will receive atezolizumab through an IV every three weeks and take vorolanib daily by mouth. Suitable candidates have small cell lung cancer and have completed three to four cycles of standard chemotherapy without cancer progression. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on chronic antiplatelet therapy (like certain blood thinners) or high doses of systemic glucocorticoids (steroids). It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that atezolizumab is generally well-tolerated. In previous studies, it was safely used to treat lung cancer. Some side effects, like tiredness or loss of appetite, can occur but are usually manageable.

Vorolanib is less familiar, but earlier studies suggest it is also safe to use. Some patients experienced mild to moderate side effects, such as high blood pressure or diarrhea, which were often controllable with standard treatments.

As this is a Phase 2 trial, the treatment has already demonstrated sufficient safety in earlier phases to warrant further testing. This indicates that the combination of vorolanib and atezolizumab is considered safe enough for continued study. However, participants must be closely monitored for any new or severe side effects. It is important to consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Vorolanib combined with Atezolizumab for small cell lung cancer because it offers a novel approach by combining an anti-angiogenic agent with an immune checkpoint inhibitor. Vorolanib targets the blood vessels that supply tumors, potentially starving the cancer cells, while Atezolizumab helps the immune system recognize and attack cancer cells. This dual action could enhance the effectiveness compared to current treatments that primarily focus on either chemotherapy or single-agent immunotherapy, offering a potential new avenue for patients who have limited options after initial treatments.

What evidence suggests that vorolanib and atezolizumab could be effective for small cell lung cancer?

Research has shown that adding atezolizumab to standard chemotherapy can improve outcomes for people with small cell lung cancer. One study found that patients who received atezolizumab lived an average of 5.2 months without cancer progression, compared to 4.3 months for those who received a placebo. In this trial, participants will receive a combination of vorolanib and atezolizumab. Vorolanib, a newer drug, is being tested for its potential to treat various cancers by blocking tumor growth pathways. The trial aims to enhance treatment effectiveness by combining vorolanib with atezolizumab, potentially prolonging the period without cancer growth. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel Morgensztern

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with extensive-stage small cell lung cancer who've had specific initial treatments without disease progression. They must have normal organ and bone marrow function, not be on certain blood thinners or antiplatelet drugs, and can't have uncontrolled high blood pressure or recent severe infections. Participants need to agree to use contraception and cannot be pregnant or breastfeeding.

Inclusion Criteria

You need to have a certain level of a type of white blood cell called neutrophils.

I agree to use birth control during and after the study and am not breastfeeding.

I've had 3-4 cycles of specific cancer treatment without my tumor growing and can start the study treatment within 6-8 weeks.

Exclusion Criteria

I do not have untreated brain metastases or brain bleeding, and I haven't had preventive brain radiation.

My high blood pressure has not been controlled with medication for over 3 weeks.

I have not coughed up a significant amount of blood recently nor does my cancer invade major blood vessels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive 3 to 4 cycles of standard-of-care induction therapy

9-12 weeks

Maintenance Treatment

Participants receive atezolizumab intravenously every 3 weeks and vorolanib by mouth daily

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Vorolanib

Trial Overview The trial is testing if adding vorolanib to atezolizumab extends the time patients remain cancer-free after standard chemotherapy. Patients will receive this combination as a maintenance therapy, which means it's used after initial treatment to help keep the cancer from coming back.

How Is the Trial Designed?

Group I: Vorolanib + Atezolizumab Experimental Treatment 2 Interventions

Consenting and eligible participants who have no evidence of tumor progression after 3 to 4 cycles of standard-of-care induction therapy will receive atezolizumab intravenously (IV) every 3 weeks and vorolanib by mouth daily.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Xcovery Holdings, Inc.

Industry Sponsor

Trials

10

Recruited

620+

Xcovery Holding Company, LLC

Industry Sponsor

Trials

9

Recruited

530+

Published Research Related to This Trial

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

In a retrospective study of 213 patients with extensive-stage small cell lung cancer (SCLC), atezolizumab combined with chemotherapy demonstrated a median progression-free survival (PFS) of 6.8 months and overall survival (OS) of 11.9 months, confirming its efficacy in a real-life setting.

The treatment was generally safe, with manageable hematological side effects, and factors like ECOG performance status and number of metastatic sites were found to influence both PFS and OS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group. Gürbüz, M., Kutlu, Y., Akkuş, E., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 518 patients with extensive small cell lung cancer (SCLC) receiving atezolizumab plus chemotherapy, the median overall survival was 11.3 months, with 46.7% of patients alive at 12 months, indicating the treatment's effectiveness in a real-world setting.

The study demonstrated that 23.6% of patients continued atezolizumab treatment beyond disease progression, suggesting a potential strategy for improving outcomes, particularly in patients with better performance status (PS 0/1) who had a median overall survival of 12.2 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. Falchero, L., Guisier, F., Darrason, M., et al.[2023]

In a study of 47 patients with transformed small-cell lung cancer (T-SCLC), combining the PD-L1 inhibitor atezolizumab with chemotherapy resulted in a high objective response rate of 73% and significantly improved overall survival (20.2 months) compared to those who did not receive immunotherapy (7.9 months).

The combination therapy was well tolerated, showing a safety profile consistent with previous studies, suggesting it could be a promising treatment option for T-SCLC patients, particularly those with positive PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. Zhang, CY., Sun, H., Su, JW., et al.[2023]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

Citations

1. clinicaltrials.eu clinicaltrials.eu/inn/vorolanib/

VOROLANIB – Application in Therapy and Current Clinical ... Vorolanib (also known as CM082 or X-82) is an emerging drug being investigated across multiple clinical trials for various cancer types.

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/69/NCT04373369/Prot_SAP_000.pdf

A phase II study of maintenance vorolanib and ... Atezolizumab is a PD-L1 blocking antibody indicated for the treatment of urothelial carcinoma, non-small cell lung cancer, triple-negative breast cancer, and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11880126/

Efficacy and safety analysis of atezolizumab continuation ... Efficacy and safety analysis of atezolizumab continuation beyond progression in extensive-stage small cell lung cancer

4. tecentriq-hcp.com tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html

IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

5. cancernetwork.com cancernetwork.com/view/atezolizumab-combo-real-world-data-match-clinical-trial-efficacy-in-sclc

Atezolizumab Combo Real-World Data Match Clinical Trial ... Atezolizumab (Tecentriq) plus carboplatin and etoposide demonstrated clinical practice efficacy in patients with extensive-stage small cell lung cancer (ES- ...

6. asco.org asco.org/about-asco/press-center/news-releases/new-study-demonstrates-improved-survival-combination-lurbinectedin-atezolizumab-extensive-stage-sclc

New Study Demonstrates Improved Survival With ... New Study Demonstrates Improved Survival With Combination of Lurbinectedin and Atezolizumab for Extensive-Stage Small Cell Lung Cancer. May 22, ...

7. ctv.veeva.com ctv.veeva.com/study/vorolanib-atezolizumab-as-maintenance-therapy-for-extensive-stage-small-cell-lung-cancer

Vorolanib + Atezolizumab as Maintenance Therapy for ... The purpose of the study is to determine whether adding vorolanib to atezolizumab will improve the length of time that participants are cancer- ...

8. clin.larvol.com clin.larvol.com/trial-detail/NCT04373369

Vorolanib + Atezolizumab as Maintenance Therapy for ... Kaplan-Meier product limit estimator will be used to estimate the overall survival rate. Up to 3 years post completion of treatment (up to 5 years). Safety and ...